Davies JA

References (3)

Title : An Esterase-like Lyase Catalyzes Acetate Elimination in Spirotetronate\/Spirotetramate Biosynthesis - Lees_2019_Angew.Chem.Int.Ed.Engl_58_2305
Author(s) : Lees NR , Han LC , Byrne MJ , Davies JA , Parnell AE , Moreland PEJ , Stach JEM , van der Kamp MW , Willis CL , Race PR
Ref : Angew Chem Int Ed Engl , 58 :2305 , 2019
Abstract : Spirotetronate and spirotetramate natural products include a multitude of compounds with potent antimicrobial and antitumor activities. Their biosynthesis incorporates many unusual biocatalytic steps, including regio- and stereo-specific modifications, cyclizations promoted by Diels-Alderases, and acetylation-elimination reactions. Here we focus on the acetate elimination catalyzed by AbyA5, implicated in the formation of the key Diels-Alder substrate to give the spirocyclic system of the antibiotic abyssomicin C. Using synthetic substrate analogues, it is shown that AbyA5 catalyzes stereospecific acetate elimination, establishing the (R)-tetronate acetate as a biosynthetic intermediate. The X-ray crystal structure of AbyA5, the first of an acetate-eliminating enzyme, reveals a deviant acetyl esterase fold. Molecular dynamics simulations and enzyme assays show the use of a His-Ser dyad to catalyze either elimination or hydrolysis, via disparate mechanisms, under substrate control.
ESTHER : Lees_2019_Angew.Chem.Int.Ed.Engl_58_2305
PubMedSearch : Lees_2019_Angew.Chem.Int.Ed.Engl_58_2305
PubMedID: 30664319
Gene_locus related to this paper: verma-f4f7f5

Title : THE CONCISE GUIDE TO PHARMACOLOGY 2019\/20: Enzymes - Alexander_2019_Br.J.Pharmacol_176 Suppl 1_S297
Author(s) : Alexander SPH , Fabbro D , Kelly E , Mathie A , Peters JA , Veale EL , Armstrong JF , Faccenda E , Harding SD , Pawson AJ , Sharman JL , Southan C , Davies JA
Ref : British Journal of Pharmacology , 176 Suppl 1 :S297 , 2019
Abstract : The Concise Guide to PHARMACOLOGY 2019/20 is the fourth in this series of biennial publications. The Concise Guide provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.14752. Enzymes are one of the six major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, ion channels, nuclear hormone receptors, catalytic receptors and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2019, and supersedes data presented in the 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
ESTHER : Alexander_2019_Br.J.Pharmacol_176 Suppl 1_S297
PubMedSearch : Alexander_2019_Br.J.Pharmacol_176 Suppl 1_S297
PubMedID: 31710714

Title : THE CONCISE GUIDE TO PHARMACOLOGY 2017\/18: Overview - Alexander_2017_Br.J.Pharmacol_174 Suppl 1_S1
Author(s) : Alexander SP , Kelly E , Marrion NV , Peters JA , Faccenda E , Harding SD , Pawson AJ , Sharman JL , Southan C , Buneman OP , Cidlowski JA , Christopoulos A , Davenport AP , Fabbro D , Spedding M , Striessnig J , Davies JA
Ref : British Journal of Pharmacology , 174 Suppl 1 :S1 , 2017
Abstract : The Concise Guide to PHARMACOLOGY 2017/18 is the third in this series of biennial publications. This version provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.13882/full. In addition to this overview, in which are identified 'Other protein targets' which fall outside of the subsequent categorisation, there are eight areas of focus: G protein-coupled receptors, ligand-gated ion channels, voltage-gated ion channels, other ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2017, and supersedes data presented in the 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature Committee of the Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
ESTHER : Alexander_2017_Br.J.Pharmacol_174 Suppl 1_S1
PubMedSearch : Alexander_2017_Br.J.Pharmacol_174 Suppl 1_S1
PubMedID: 29055037